Self-healing gel can be injected into the body and act as a long-term drug depot
SEM images, taken at different magnifications, show the structure of new nanoparticle hydrogels interacting with long polymer chains.
Scientists are keen to use gels to deliver drugs because they can be moulded into specific shapes and designed to release their payload during a specified time period. However, current versions aren’t always practical because they must be implanted surgically.
To help overcome this obstacle, chemical engineers from MIT have designed a new type of self-healing hydrogel that could be injected through a syringe. Such gels, which can carry one or two drugs at a time, could be used to treat cancer, macular degeneration or heart disease, say the researchers.
The new gel consists of a mesh network made of two components: nanoparticles made of polymers entwined within strands of another polymer, such as cellulose. ‘Now you have a gel that can change shape when you apply stress; and then, importantly, it can reheal when you relax those forces,’ notes Mark Tibbitt from MIT’s Koch Institute for Integrative Cancer Research.
Scientists have previously constructed hydrogels for biomedical use by forming irreversible chemical linkages between polymers. These gels, used to make soft contact lenses, for example, are tough and sturdy, but once they are formed their shape cannot easily be altered.
The MIT team set out to create a gel that could survive strong mechanical (shear) forces and then reform itself. Other researchers have created such gels by engineering proteins that self-assemble into hydrogels, but this approach requires complex biochemical processes. The MIT team wanted to design something simpler.
The MIT approach relies on a combination of two readily available components. One is a type of nanoparticle formed of PEG-PLA copolymers. To form a hydrogel, the researchers mixed these particles with a polymer — in this case, cellulose.
Each polymer chain forms weak bonds with many nanoparticles, producing a loosely woven lattice of polymers and nanoparticles. Because each attachment point is fairly weak, the bonds break apart under mechanical stress, such as when injected through a syringe. When the shear forces are removed, the polymers and nanoparticles form new attachments with different partners, healing the gel.
Using two components to form the gel also gives the researchers the opportunity to deliver two different drugs at the same time. PEG-PLA nanoparticles have an inner core that is ideally suited to carry hydrophobic small-molecule drugs, which include many chemotherapy drugs. Meanwhile, the polymers, which exist in a watery solution, can carry hydrophilic molecules such as proteins, including antibodies and growth factors.
Long-term drug delivery
In a recent study, the researchers showed that the gels survived injection under the skin of mice and successfully released two drugs, one hydrophobic and one hydrophilic, for several days.
This type of gel offers an important advantage compared with injecting a liquid solution of drug-delivery nanoparticles. Although a solution will immediately disperse throughout the body, the gel stays in place after injection, allowing the drug to be targeted to a specific tissue.
Furthermore, the properties of each gel component can be tuned so that the drugs they carry are released at different rates, allowing them to be tailored for different uses.